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WT1 protein is a transcriptional activator of the antiapoptotic bag3 gene

Leukemia volume 24, pages 1204–1206 (2010)Cite this article

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WT1 gene, originally identified as a tumor suppressor involved in the formation of Wilms' tumor of the kidney, was subsequently described to have an oncogenic role in a variety of tumors from different origins, including leukemias.1 In comparison to normal progenitor cells, it is overexpressed in acute lymphoblastic and myeloblastic leukemia, and in the blast crisis phase of chronic myelogenous leukemia;1, 2 high levels of the protein are associated with a poor response to therapy.1, 3 WT1 knockdown by antisense oligonucleotides or RNA interference was shown to induce apoptosis; conversely, its overexpression in myeloid leukemia cells protected against cell death. Modulation of some members of the bcl-2 family has been associated with apoptosis inhibition by WT1.1, 3

Among proteins that regulate apoptosis in leukemia cells, a role is assigned to BAG3, a member of the family of proteins that, through their BAG domain, interact with HSC70/HSP70 heat shock proteins. bag3 gene expression is constitutive in some tumor types, including leukemias; in these cells, BAG3 protein has been shown to sustain cell survival and downmodulate cell apoptotic response to drugs, by either HSP70-dependent or -independent mechanisms.4, 5, 6, 7

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Acknowledgements

This work was supported in part by funds of Italian Ministry of University and Research (MIUR).

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  1. E Cesaro and G Montano: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Medical Biotechnology, University of Naples, Naples, Italy

    E Cesaro, G Montano, R Crescitelli, P Izzo & P Costanzo

  2. Division of Biomedicine, Department of Pharmaceutical Sciences (DiFarma), University of Salerno, Salerno, Italy

    A Rosati & M C Turco

  3. BioUniverSA srl, Salerno, Italy

    A Rosati & M C Turco

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  1. E Cesaro
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Correspondence to M C Turco.

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Cesaro, E., Montano, G., Rosati, A. et al. WT1 protein is a transcriptional activator of the antiapoptotic bag3 gene. Leukemia 24, 1204–1206 (2010). https://doi.org/10.1038/leu.2010.68

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